The first objective of the proposed work is to conduct a bidirectional selective breeding project to produce three lines of mice which differ markedly from one another in their genetically-based sensitivity to the analgesic (antinociceptive) effects of opiate drugs (narcotic analgesics). To this end, three selection lines will be formed from a genetically heterogeneous foundation population: one will be selectively bred for a high antinociceptive response, another for a low antinociceptive response, and the third will be a (nonselected) control line. Selection will be based on hind paw-lick latencies on the hot plate assay in response to levorphanol. Once these three lines have diverged greatly in their sensitivity to opioid-induced antinociception, studies will then be conducted to determine the biochemical mechanisms which account for the selection line differences, and a search made for other effects of opiods which may share common mechanisms with the antinociceptive response. These animals should be a valuable resource for research concerning the actions of analgesic drugs and mechanisms of pain in general. Every reasonable effort will be made to make these selection lines available to other investigators who might wish to use them.